Biotechnology Letters

, Volume 40, Issue 9–10, pp 1425–1433 | Cite as

Forced expression of CD200 improves the differentiation capability and immunoregulatory functions of mesenchymal stromal cells

  • Hye Joung Kim
  • Kyoung-Woon Kim
  • Yong-Rim Kwon
  • Bo-Mi Kim
  • Yoo-Jin KimEmail author
Original Research Paper



In order to identify specific mesenchymal stromal cell (MSC) populations with enhanced therapeutic efficacy, we evaluated the functional changes associated with the stable expression of CD200, which is associated with immune regulatory function and osteogenic differentiation, in human bone marrow-derived MSCs (CD200/MSCs).


We detected significantly greater osteogenesis and chondrogenesis in CD200/MSCs than in mock-transfected MSCs. In addition, the immune regulatory function of MSCs in mixed lymphocyte reactions was enhanced by CD200 gene transfection. In CD200/MSCs, the secretion of inflammatory cytokines, i.e., IL-6 and IL-8, was reduced, and levels of the anti-inflammatory factors IL-10, FOXP3, and indoleamine 2,3-dioxygenase 1 were elevated. Finally, CD200 transfection increased the stemness of MSCs, as evidenced by greater colony numbers in colony-forming unit fibroblast assays and analyses of NANOG and OCT-4 expression.


These results suggest that CD200/MSCs have therapeutic applications, and further in-depth research should focus on the development of a clinically applicable cell-based therapeutic strategy.


Adipogenesis CD200 Chondrogenesis Immune regulation Mesenchymal stromal cells Osteogenesis 



This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Grant Nos. 2015R1A2A2A04002756 and 2018R1A2B2006820). It was also supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (Grant Nos. 2010-0008762, 2014R1A1A3054664).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Alvarez-Lara MA, Carracedo J, Ramírez R, Martín-Malo A, Rodríguez M, Madueño JA, Aljama P (2004) The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1 subset. Nephrol Dial Transplant 19(12):3084–3090CrossRefPubMedGoogle Scholar
  2. Chen Y, Song Y, Miao H, Xu Y, Lv M, Wang T, Hou Y (2015) Gene delivery with IFN-gamma-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis. Inflamm Res 64(9):671–681CrossRefPubMedGoogle Scholar
  3. Cherwinski HM, Murphy CA, Joyce BL, Bigler ME, Song YS, Zurawski SM, Moshrefi MM, Gorman DM, Miller KL, Zhang S, Sedgwick JD, Phillips JH (2005) The CD200 receptor is a novel and potent regulator of murine and human mast cell function. J Immunol 174(3):1348–1356CrossRefPubMedGoogle Scholar
  4. Daneshmandi S, Karimi MH, Pourfathollah AA (2017) TGF-beta engineered mesenchymal stem cells (TGF-β/MSCs) for treatment of Type 1 diabetes (T1D) mice model. Int Immunopharmacol 44:191–196CrossRefPubMedGoogle Scholar
  5. Dazzi F, Lopes L, Weng L (2012) Mesenchymal stromal cells: a key player in ‘innate tolerance’? Immunology 137(3):206–213CrossRefPubMedPubMedCentralGoogle Scholar
  6. Delorme B, Ringe J, Gallay N, Le Vern Y, Kerboeuf D, Jorgensen C, Rosset P, Sensebé L, Layrolle P, Häupl T, Charbord P (2008) Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells. Blood 111(5):2631–2635CrossRefPubMedGoogle Scholar
  7. Kim N, Cho SG (2015) New strategies for overcoming limitations of mesenchymal stem cell-based immune modulation. Int J Stem Cells 8(1):54–68CrossRefPubMedPubMedCentralGoogle Scholar
  8. Kim HJ, Kwon YR, Bae YJ, Kim YJ (2016) Enhancement of human mesenchymal stem cell differentiation by combination treatment with 5-azacytidine and trichostatin A. Biotechnol Lett 38(1):167–174CrossRefPubMedGoogle Scholar
  9. Lee L, Liu J, Manuel J, Gorczynski RM (2006) A role for the immunomodulatory molecules CD200 and CD200R in regulating bone formation. Immunol Lett 105(2):150–158CrossRefPubMedGoogle Scholar
  10. Min CK, Kim BG, Park G, Cho B, Oh IH (2007) IL-10-transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation. Bone Marrow Transplant 39(10):637–645CrossRefPubMedGoogle Scholar
  11. Mohanty S, Kumar A, Dhawan J, Sharma VK, Gupta S (2013) Depletion of CD200+ Hair Follicle Stem Cells in Human Prematurely Gray Hair Follicles. J Cutan Aesthet Surg 6(2):90–92CrossRefPubMedPubMedCentralGoogle Scholar
  12. Payne NL, Dantanarayana A, Sun G, Moussa L, Caine S, McDonald C, Herszfeld D, Bernard CC, Siatskas C (2012) Early intervention with gene-modified mesenchymal stem cells overexpressing interleukin-4 enhances anti-inflammatory responses and functional recovery in experimental autoimmune demyelination. Cell Adhes Migr 6(3):179–189CrossRefGoogle Scholar
  13. Pietilä M, Lehtonen S, Tuovinen E, Lähteenmäki K, Laitinen S, Leskelä HV, Nätynki A, Pesälä J, Nordström K, Lehenkari P (2012) CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells. PLoS ONE 7(2):e31671CrossRefPubMedPubMedCentralGoogle Scholar
  14. Pontikoglou C, Langonné A, Ba MA, Varin A, Rosset P, Charbord P, Sensébé L, Deschaseaux F (2016) CD200 expression in human cultured bone marrow mesenchymal stem cells is induced by pro-osteogenic and pro-inflammatory cues. J Cell Mol Med 20(4):655–665CrossRefPubMedPubMedCentralGoogle Scholar
  15. Rostovskaya M, Anastassiadis K (2012) Differential expression of surface markers in mouse bone marrow mesenchymal stromal cell subpopulations with distinct lineage commitment. PLoS ONE 7(12):e51221CrossRefPubMedPubMedCentralGoogle Scholar
  16. Salem HK, Thiemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28(3):585–596PubMedGoogle Scholar
  17. Suh N, Subramanyam D, Lee M-Y (2017) Molecular signatures of secretomes from mesenchymal stem cells: therapeutic benefits. Mol Cell Toxicol 13(2):133–141CrossRefGoogle Scholar
  18. Xu L, Liu Y, Sun Y, Wang B, Xiong Y, Lin W, Wei Q, Wang H, He W, Wang B, Li G (2017) Tissue source determines the differentiation potentials of mesenchymal stem cells: a comparative study of human mesenchymal stem cells from bone marrow and adipose tissue. Stem Cell Res Ther 8(1):275CrossRefPubMedPubMedCentralGoogle Scholar
  19. Xue L, Zenlong W, Zhalun L, Chen Q, Peng Z, Haiwen C, Ziming W (2017) RBPJ contributes to acquire docetaxel resistance in prostate cancer cells. Mol Cell Toxicol 13(3):279–285CrossRefGoogle Scholar
  20. Zhang S, Cherwinski H, Sedgwick JD, Phillips JH (2004) Molecular mechanisms of CD200 inhibition of mast cell activation. J Immunol 173(11):6786–6793CrossRefPubMedGoogle Scholar
  21. Zhang J, Zhou S, Zhou Y, Feng F, Wang Q, Zhu X, Ai H, Huang X, Zhang X (2014) Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model. PLoS ONE 9(12):e114670CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Hye Joung Kim
    • 1
    • 2
  • Kyoung-Woon Kim
    • 2
  • Yong-Rim Kwon
    • 1
    • 2
  • Bo-Mi Kim
    • 2
  • Yoo-Jin Kim
    • 1
    • 2
    • 3
    • 4
  1. 1.Laboratory of Hematological Disease and Transplant ImmunologySeoulKorea
  2. 2.Department of HematologyConvergent Research Consortium for Immunologic DiseaseSeoulKorea
  3. 3.Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeoulKorea
  4. 4.Leukemia Research Institute, College of MedicineThe Catholic University of KoreaSeoulKorea

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